tbuckley/cabot-search huggingface dataset:
Higher Maternal Levels of Free Estradiol in First Compared to Second Pregnancy: Early Gestational Differences&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Bernstein, Leslie, Depue, Robert H., Ross, Ronald K., Judd, Howard L., Pike, Malcolm C., Henderson, Brian E.
Journal: JNCI Journal of the National Cancer Institute (1986)

Journal Article Higher Maternal Levels of Free Estradiol in First Compared to Second Pregnancy: Early Gestational Differences Get access Leslie Bernstein, Ph.D., Leslie Bernstein, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert H. Depue, Ph.D., Robert H. Depue, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ronald K. Ross, M.D., Ronald K. Ross, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Howard L. Judd, M.D., Howard L. Judd, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Malcolm C. Pike, Ph.D., Malcolm C. Pike, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Brian E. Henderson, M.D. Brian E. Henderson, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 76, Issue 6, June 1986, Pages 1035–1039, https://doi.org/10.1093/jnci/76.6.1035 Published: 01 June 1986 Article history Received: 03 July 1985 Revision received: 02 January 1986 Accepted: 30 January 1986 Published: 01 June 1986
Monitoring autochthonous lung tumors induced by somatic CRISPR gene editing in mice using a secreted luciferase
Authors: Nastasja Merle, Sabrina Elmshäuser, Florian Strassheimer, Michael Wanzel, Alexander M. König, Julianne Funk, Michelle Neumann, Katharina Kochhan, Frederik Helmprobst, Axel Pagenstecher, Andrea Nist, Marco Mernberger, André Schneider, Thomas Braun, Tilman Borggrefe, Rajkumar Savai, Oleg Timofeev, Thorsten Stiewe
Journal: Molecular Cancer (2022)

Abstract Background In vivo gene editing of somatic cells with CRISPR nucleases has facilitated the generation of autochthonous mouse tumors, which are initiated by genetic alterations relevant to the human disease and progress along a natural timeline as in patients. However, the long and variable, orthotopic tumor growth in inner organs requires sophisticated, time-consuming and resource-intensive imaging for longitudinal disease monitoring and impedes the use of autochthonous tumor models for preclinical studies. Methods To facilitate a more widespread use, we have generated a reporter mouse that expresses a Cre-inducible luciferase from Gaussia princeps (GLuc), which is secreted by cells in an energy-consuming process and can be measured quantitatively in the blood as a marker for the viable tumor load. In addition, we have developed a flexible, complementary toolkit to rapidly assemble recombinant adenoviruses (AVs) for delivering Cre recombinase together with CRISPR nucleases targeting cancer driver genes. Results We demonstrate that intratracheal infection of GLuc reporter mice with CRISPR-AVs efficiently induces lung tumors driven by mutations in the targeted cancer genes and simultaneously activates the GLuc transgene, resulting in GLuc secretion into the blood by the growing tumor. GLuc blood levels are easily and robustly quantified in small-volume blood samples with inexpensive equipment, enable tumor detection already several months before the humane study endpoint and precisely mirror the kinetics of tumor development specified by the inducing gene combination. Conclusions Our study establishes blood-based GLuc monitoring as an inexpensive, rapid, high-throughput and animal-friendly method to longitudinally monitor autochthonous tumor growth in preclinical studies.
ThermoTRP channels in pain sexual dimorphism: new insights for drug intervention
Authors: David Cabañero, Eva Villalba-Riquelme, Gregorio Fernández-Ballester, Asia Fernández-Carvajal, Antonio Ferrer-Montiel
Journal: Pharmacology & Therapeutics (2022)

Chronic pain is a major burden for the society and remains more prevalent and severe in females. The presence of chronic pain is linked to persistent alterations in the peripheral and the central nervous system. One of the main types of peripheral pain transducers are the transient receptor potential channels (TRP), also known as thermoTRP channels, which intervene in the perception of hot and cold external stimuli. These channels, and especially TRPV1, TRPA1 and TRPM8, have been subjected to profound investigation because of their role as thermosensors and also because of their implication in acute and chronic pain. Surprisingly, their sensitivity to endogenous signaling has been far less studied. Cumulative evidence suggests that the function of these channels may be differently modulated in males and females, in part through sexual hormones, and this could constitute a significant contributor to the sex differences in chronic pain. Here, we review the exciting advances in thermoTRP pharmacology for males and females in two paradigmatic types of chronic pain with a strong peripheral component: chronic migraine and chemotherapy-induced peripheral neuropathy (CIPN). The possibilities of peripheral druggability offered by these channels and the differential exploitation for men and women represent a development opportunity that will lead to a significant increment of the armamentarium of analgesic medicines for personalized chronic pain treatment.
Long-term follow-up of patients with chronic hepatitis C treated with different doses of interferon-α2b
Authors: Giorgio Saracco, Floriano Rosina, Maria Lorena Abate, Livio Chiandussi, Vittorio Gallo, Elena Cerutti, Angelo Di Napoli, Antonio Solinas, Angelo Deplano, Andreina Tocco, Pierangela Cossu, David Chien, George Kuo, Alan Polito, Amy J. Weiner, Michael Houghton, Giorgio Verme, Ferruccio Bonino, Mario Rizzetto
Journal: Hepatology (1993)

Eighty patients with chronic hepatitis C who completed a previously reported randomized controlled trial on the efficacy of interferon-α 2b were followed up for at least 36 mo after therapy discontinuation. Seventeen patients (21.2%) maintained normal ALT values throughout the follow-up; 63 (78.8%) either did not normalize the levels of ALT or relapsed during the follow-up. A significantly greater proportion of patients treated with 3 million units of interferon three times a week subcutaneously for 48 wk were long-term responders compared with patients treated for 24 wk. Sex, age, hepatitis C virus antibody status, source of infection and pretreatment levels of ALT were not predictive of long-term response. Cirrhosis was found to be an unfavorable predictive factor. After 3 yr of follow-up, clearance of viremia was observed in 58.9% of the 17 long-term responders but in none of the nonresponders (p = 0.002). E2-NS1 antibody tested negative in 88.2% of long-term responders and in 14.3% of nonresponders (p = 0.001). Fifty-nine percent of long-term responders tested negative for C100-NS4 antibody compared with 14.3% of nonresponders (p = 0.031). No significant change was observed in other antibodies. Four long-term responders underwent liver biopsy 2 yr after discontinuation of therapy. All four patients had normal liver histology compared with baseline assessment of chronic active hepatitis in three and chronic persistent hepatitis in the other. Three of the four were negative for serum hepatitis C virus RNA. (HEPATOLOGY 1993; 18:1300-1305.)
Polymyositis Associated With Malignant Histiocytosis
Authors: Francisco Perez-Jimenez
Journal: JAMA (1981)

SINCE Wagner's original description in 1863, dermatomyositis has been associated with different neoplastic conditions, including leukemias and lymphomas.<sup>1-4</sup>Thus far, we have been unable to find any other report of polymyositis associated with malignant histiocytosis (MH). <h3>Report of a Case</h3> A 62-year-old man was admitted to our hospital on April 23, 1979, because of fever and a rash. He had been treated with sulfonamides and chloramphenicol because of suspected typhoid fever. The workup was not diagnostic. The rash cleared, and the fever subsided. Serum enzyme levels are shown in the Table. A tentative diagnosis of hypersensitivity angiitis secondary to sulfonamide therapy and possible brucellosis was made, and the patient was discharged quite improved. Three months later the fever recurred, and severe pain in both calves appeared together with anorexia, weight loss, and low back pain. The patient was readmitted for further treatment. The liver and spleen were felt at
The Changing Indications for Excretory Urography
Authors: Rajendra Kumar
Journal: JAMA (1985)

EXCRETORY urography (EU) is considered the first and foremost radiological procedure in the evaluation of the urinary tract. However, with experience and the emergence of newer imaging modalities, the role of EU needs reevaluation in the diagnostic studies of patients in many clinical situations. Numerous reports have appeared in the literature detailing the low yield of EU in certain clinical settings. Despite repeated condemnation of routine EU in conditions where its role is questionable, no decrease in the overall numbers of this procedure has been observed; teaching hospitals may be an exception. Approximately 4 million excretory urograms are performed in this country every year, with a total cost of over a half billion dollars.<sup>1</sup>Most of these examinations are accomplished in physicians' offices and nonteaching hospitals. Whether excretory urograms really are indicated in so large a group of patients is questionable and controversial. Escalating medical costs make it imperative
Highlights of This Issue
Journal: Clinical Cancer Research (2011)

Peritoneal carcinomatosis is a frequent cause of death in patients with advanced gastric cancer. Here, Yasumoto and colleagues investigated whether EGFR ligands and/or the ErbB family of receptors are involved in the development of this condition. They found that the EGFR ligands amphiregulin and HB-EGF collaborated with the CXCR4/CXCL12 axis to promote peritoneal carcinomatosis by stimulating the migration, proliferation, and survival of CXCR4-expressing gastric cancer cells and stromal fibroblasts. Furthermore, these two EGFR ligands showed different biological activities in target cells. These findings provide a framework for future clinical trials of ErbB receptor inhibitors that target tumor cells and their environment.Metastases can differ greatly from primary tumor tissue in terms of genetic characteristics. However, taking biopsies from metastases in patients is an invasive procedure and is frequently not possible due to the lack of accessible lesions. Circulating tumor cells (CTCs) are found in the peripheral blood of patients and can thus be regarded as “liquid biopsies” of metastasizing cells. In this study, Sieuwerts and colleagues demonstrate the feasibility of performing an extensive molecular characterization of CTCs from breast cancer patients at both the mRNA and microRNA level. It is anticipated that this approach will improve currently available prognostic and predictive models.Growing evidence suggests that chronic stress can promote cancer growth and progression. In this study, Moreno-Smith and colleagues show that dopamine can block the stimulatory effects of chronic stress on ovarian cancer tumor growth. They found that dopamine retards tumor growth by inhibiting tumor angiogenesis and stimulating tumor cell apoptosis. Further, dopamine depletion during chronic stress created a permissive microenvironment for tumor growth that could be reversed by dopamine replacement. Based on these findings, dopamine analogues may represent a novel therapeutic strategy for blocking the deleterious effects of chronic stress.Host immune reactivity to Pseudomonas exotoxin (PE)-based immunotoxins limits the ability to deliver repetitive immunotoxin doses that are needed for optimal anticancer effects. Here, Mossoba and coworkers show that administration of pentostatin plus cyclophosphamide in a murine model safely depleted host lymphocytes and abrogated host capacity to form antibodies to a PEbased immunotoxin through nine consecutive immunotoxin doses. These results suggest that novel host preparative therapy, such as the pentostatin plus cyclophosphamide regimen, represents an approach to deliver prolonged immunotoxin therapy for enhanced anticancer effects against a wide range of malignancies.
The Place of Irradiation
Authors: Eric Riches
Journal: JAMA (1968)

The dogma of radioresistance of cancer of the kidney is unacceptable. No patient has been "cured" by radiotherapy alone, but an adequate dose cannot be given to the kidney without damaging adjacent structures. Tumors vary in radiosensitivity according to their anaplasia and oxygenation. Some respond to irradiation. In one series,<sup>43</sup>the five-year survival of 362 inoperable patients who were left untreated was 0.5%; in 83 who were treated by radiotherapy, it was 6%. <h3>Postoperative Irradiation</h3><h3>Results.—</h3> Local irradiation after nephrectomy is used frequently. In the British Association of Urological Surgeons' series,<sup>43</sup>the 5- and 10-year survivals in potentially curable patients were 30% and 17% after nephrectomy. With added postoperative irradiation, they were 49% and 27%. The gain was greatest in those with renal vein invasion. Flocks and Kadesky<sup>44</sup>found similar improvement. In my series, 36 of 100 received postoperative irradiation. Improvement beyond three years was achieved only
Neurocardiogenic Syncope
Authors: V K Somers, F M Abboud
Journal: New England Journal of Medicine (1998)

Most physiologic reflex mechanisms subserve obvious and logical purposes. For example, the arterial baroreflex responds to hypotension by eliciting tachycardia and vasoconstriction, thus increasing cardiac output and raising blood pressure. The raison d'etre for a reflex such as the Bezold-Jarisch is not immediately apparent. Consider, however, the predominant stimulus for the Bezold-Jarisch reflex in the clinical context, namely, rapid forceful ventricular contraction around a relatively empty chamber. Allowing such a situation to continue would be counterproductive. Decreased diastolic filling time, regardless of ventricular contractility, would not permit any improvement in forward cardiac output and hence lead to even further hypotension and thus increasing tachycardia and adrenergic drive to the heart. The cardiac inhibitory reflex acts as a "safety valve," so to speak, slowing the heart rate, increasing diastolic filling, and decreasing afterload. This would be beneficial in myocardial infarction and aortic stenosis. In some persons, however, the reflex may be potentiated, thus predisposing to neurally mediated syncope with relatively minor provocation. We have attempted to explore the role of the cardiac inhibitory reflex in syncope associated with several clinical situations. The advent of direct measurements of sympathetic activity by microneurography, together with the availability of provocative testing such as upright tilt and programmed electrical cardiac stimulation, has provided much new insight but has also given rise to a host of additional questions. Mechanisms other than the Bezold-Jarisch reflex may be implicated. Induction of vasodepressor syncope in heart transplant recipients, as well as the association of bradycardia and syncope with partial seizures, provides some evidence that left ventricular mechanoreceptors may not be the exclusive afferent trigger for syncope and that central mechanisms may be implicated. The study of biochemical mediators such as nitric oxide and serotonin, acting perhaps at a central level, holds promise for an increased understanding of basic cardiovascular physiology, as well as for effective therapy for neurally mediated syncope. These biochemical mediators may in and of themselves give rise to neurogenic syncope or may act to increase the gain of the cardiac inhibitory reflex at a central level.
Increasing Trends of Multiple Myeloma Mortality in England and Wales; 1950–79: Are the Changes Real?&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: Velez, Ramon, Seral, Valerie, Cuzick, Jack
Journal: JNCI Journal of the National Cancer Institute (1982)

Journal Article Increasing Trends of Multiple Myeloma Mortality in England and Wales; 1950–79: Are the Changes Real? Get access Ramon Velez, M.D., M.Sc., Ramon Velez, M.D., M.Sc. 5 5Address reprint requests to Dr. Velez, HSR & D and Clinical Epidemiology Unit, Durham Veterans Administration Medical Center, 508 Fulton St., Durham, N.C. 27705. Search for other works by this author on: Oxford Academic PubMed Google Scholar Valerie Seral, M.R.C.P., Valerie Seral, M.R.C.P. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jack Cuzick, Ph.D. Jack Cuzick, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 69, Issue 2, August 1982, Pages 387–392, https://doi.org/10.1093/jnci/69.2.387 Published: 01 August 1982 Article history Received: 27 October 1981 Accepted: 26 February 1982 Published: 01 August 1982
Life, Death, and the Dollar Sign
Authors: Dana E. Johnson
Journal: JAMA (1984)

A NEW set of abbreviations is rapidly becoming part of the practicing physician's vocabulary. DRGs, HMOs, PPOs—the letters that denote the strategies developed to contain rising medical costs also connote a profound and rapid shift in the manner in which medical care is delivered. The extent to which these abbreviations pervade the medical and lay press leaves little doubt of their certain effects on the routine practice of medicine. However, these proposals also have the potential to insidiously alter the factors considered in making life-and-death decisions for individual patients. That these difficult decisions on whether to withhold or provide costly life-sustaining support may be based strongly on financial considerations may soon become a realistic possibility, if not a probability. How does one factor life and death in the new ledger of economic restraint? Cost-containment mechanisms will not only strain the financial acumen of physicians and medical administrators but may test
A New Curare Test for the Diagnosis of Myasthenia Gravis
Authors: Francis F. Foldes
Journal: JAMA (1968)

A simple, safe, and reliable curare test for the diagnosis of myasthenia gravis, based on the increased sensitivity of persons with myasthenia to tubocurarine, consists of the recording of the grip strength before and after the regional intravenous administration of 0.2 mg of tubocurarine. The only special equipment required is a dynamometer. The injection of 0.2 mg tubocurarine caused a 67.9 ± 7.0% and a 10.0 ± 3.9% decrease of grip strength in patients with generalized myasthenia and normal subjects, respectively. Patients with purely ocular myasthenia gravis behaved as normal subjects. The test gives positive results in cases of myasthenia gravis in which the edrophonium chloride test is negative. Because of its safety and simplicity, the test with tubocurarine is preferable to the conventional curare test.
Immunoadjuvant Effects of &lt;italic&gt;Blastomyces dermatitidis&lt;/italic&gt; Against EL 4 Lymphoma in C57BL/6J Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: McDaniel, L. Scott, Cozad, George C.
Journal: JNCI Journal of the National Cancer Institute (1982)

Journal Article Immunoadjuvant Effects of Blastomyces dermatitidis Against EL 4 Lymphoma in C57BL/6J Mice Get access L. Scott McDaniel, L. Scott McDaniel Address reprint requests to Dr. McDaniel Search for other works by this author on: Oxford Academic PubMed Google Scholar George C. Cozad George C. Cozad Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 69, Issue 6, December 1982, Pages 1337–1342, https://doi.org/10.1093/jnci/69.6.1337 Published: 01 December 1982 Article history Received: 01 February 1982 Revision received: 28 May 1982 Accepted: 04 August 1982 Published: 01 December 1982
Composite Operations and Reconstruction
Authors: F. X. Paletta
Journal: JAMA (1971)

The present concept regarding defects of the head and neck that are created by cancer therapy is that they require immediate reconstruction. Prior to 1940, the majority of extensive tumors in this region were treated by radiation or cautery. Restoration of the area destroyed by invading cancer cells or therapy was delayed for six months or more. The reason for the delay in repair was to make sure that there was no recurrence of tumor. Many patients walked around with large, unsightly, smelly defects of the face covered by a patchy dressing. Treatment today is directed to a "definitive plan" of management; it may fall into four categories: (1) radiation, (2) combined radiation and surgery, (3) surgery alone, and (4) chemotherapy. The decision of plan to be outlined must come from the "inventory analysis" made about the patient and the tumor. Since there is no laboratory test to evaluate the
Low CSF Glucose Level (Hypoglycorrhachia) in Symptomatic Hypoglycemia
Authors: Allen B. Gruber
Journal: JAMA (1982)

IT IS well known that hypoglycemia can produce focal neurological signs mimicking acute cerebrovascular disease.<sup>1,2</sup>But ascertainment of the diagnosis of transient hypoglycemia may often be difficult. The following case illustrates the utility of CSF glucose levels in establishing pathogenesis, based on delayed and prolonged depression of CSF glucose when serum glucose is depressed only transiently. <h3>Report of a Case</h3> A right-handed 84-year-old woman, with a history of treated hypertension, came to the St Louis City Hospital emergency room (Figure, point 1) "confused" and with "slurred speech," noticed since the previous evening. She was awake and somewhat agitated and had nonfluent aphasia. She could name common objects and repeat, "It's a pretty day," but had difficulty repeating "no ifs, ands, or buts." There was difficulty in following detailed commands. The remainder of the neurological and medical examination results were unremarkable. In the emergency room, serum chemistry determinations were as
Highlights from Recent Cancer Literature
Journal: Cancer Research (2017)

CMTM6 Is a Master Regulator of PD-L1 ExpressionThe interaction between PD-1 on T cells and PD-L1 on tumor cells inhibits activation, expansion, and effector functions of antigen-specific CD8 þ T cells, helping cancer cells evade immune destruction.To define how surface expression of PD-L1 is maintained, Burr and colleagues employed a genome-wide CRISPR-Cas9 screen.They identified CMTM6, a previously uncharacterized protein, as a critical regulator of PD-L1 surface expression in cancer cells.CMTM6 functions through binding to PD-L1, ensuring its recycling back to the plasma membrane and away from lysosome-mediated degradation.Importantly, depletion of CMTM6 led to decreased cell surface PD-L1 expression, alleviating suppression of tumorspecific T-cell activity in vitro and in vivo, leading to reduced tumor growth.These findings identify a previously unrecognized master regulator of this critical immune checkpoint and highlight a potential therapeutic target to overcome immune evasion by tumor cells.(Image courtesy of